G Protein β3 Subunit Gene C825T Polymorphism and its Association with the Presence and Clinicopathological Characteristics of Prostate Cancer

Abstract

A C825T polymorphism in the GNB3 gene encodes the Gβ3 subunit of heterotrimeric G proteins. Due to increased G protein activation the GNB3 825T allele, a truncated form of the G3 protein, is associated with enhanced signal transduction capacity. This splice variant is associated with various malignant diseases. We investigated the possible association of GNB3 gene polymorphism with prostate cancer and its clinicopathological characteristics. Using polymerase chain reaction and restriction fragment length polymorphism the allele frequency of the C825T polymorphism was investigated in 172 patients with prostate cancer. Results were compared with those of 344 age matched, healthy blood donors. The frequency of the GNB3 825T allele in patients with prostate cancer was significantly higher than in controls (49.1% vs 42.7%, OR 3.76, p = 0.003). Patients with prostate cancer who had the TT genotype were at 2.52 times higher risk for prostate cancer than the CC genotype referent group (OR 2.22, 95% CI 1.18-4.22, p = 0.008). Accordingly a significant increased risk of advanced disease was observed in men carrying the GNB3 TT genotype compared with those homozygous for the wild-type C allele (OR 6.24, 95% CI 4.16-12.45, p = 0.001). Men lacking the C825 allele were at approximately sevenfold higher risk for high grade (Gleason score greater than 7) prostate cancer than men with the GNB3 CC genotype. Our study presents preliminary but intriguing data suggesting that GNB3 gene polymorphism influences susceptibility to prostate cancer.